The Coulombe Lab

Translational Proteomics Research Unit @ IRCM

MISSION

The Coulombe lab is an open science ecosystem where basic scientists and clinical researchers, from the academic or private sectors, collaborate to i) characterize molecular defects that cause rare genetic diseases, ii) identify biomarkers to pre-diagnose patient phenotypes, and iii) discover drugs that will ultimately generate affordable medicines for patients everywhere.

ACTIVE PROJECTS

Unraveling the molecular basis of novel forms of hypomyelinating leukodystrophies (CIHR, Lead G. Bernard MUHC).
A biomarker discovery pipeline for precision medicine (Government of Quebec/IRCM, Lead B. Coulombe IRCM).
A patient-derived iPSC platform of disease relevant cell models for biological studies (ALS Canada and Brain Canada, Lead G. Rouleau MNIH).
Deciphering breast cancer HER2-negativity with regard to HER2-targeted therapy (CIHR, Lead F. Durocher, U Laval).
A machine learning approach to decipher protein-protein interactions in human plasma (IVADO and Genome Québec, Lead B. Coulombe IRCM).
Modulation of protein interactions by the Superoxide Dismutase 1 (SOD1) (supported by Atomwise Inc, Lead B. Coulombe IRCM).
The soluble fragment of neuroligin-1 as a blood biomarker of prodromal Alzheimer’s disease (Weston Brain Institute, Lead J. Brouillette HSCM).
Characterization of neuro-muscular junctions in ALS patients (ALS Canada, Lead R. Robitaille, U Montreal).
Reducing the activity of the phosphatase STEP to improve memory performance during aging (CIHR, Lead J. Brouillette HSCM).
Screening of chemical compounds that correct assembly defects of RNA polymerase III carrying a leukodystrophy-causing mutation (Leukodystrophy’s Foundation, Lead B. Coulombe IRCM).

OUR FLAGSHIP PROJECTS AND TECHNOLOGIES

THE RARE DISEASE CELL MAP

Affinity Purification coupled with Mass Spectrometry (AP-MS) and Proximity-Dependent Protein Identification (BioID)

Proteins rarely work alone, they rather associate with other proteins to exert their function. The Rare Disease Cell Map is a comprehensive repository of protein-protein interactions formed by rare disease-causing gene products and their modulation in response to causative mutations. Some data are already available on the Open for Rare website at OpenforRare.com

A BIOMARKER DISCOVERY PIPELINE FOR PRECISION MEDICINE

Quantitative proteomics (TMT, PAC-qMS)

Quantitative proteomics is a methodology of choice to discover biomarkers and monitor their levels in various samples. We privilege Tandem Mass Tag (TMT) to perform unbiased identification of proteins that are differentially expressed in various samples (discovery proteomics). Protein Affinity Capture coupled to quantitative Mass Spectrometry (PAC-qMS) is rather used to precisely quantify levels of a selected protein and posttranslational modifications in various samples.

Phage Display Peptide Library Screening

Identification of peptides that bind to specific proteins and protein domains is a powerful tool in biomedical research. Smith and Winter were awarded the 2018 Nobel Prize in Chemistry for the phage display of peptides and antibodies. Notably, binding of peptides to a protein of interest can either impair its activity or stabilize it interactions with other proteins. As a consequence, phage display can be a useful tool in the drug discovery process.